The objectives of the proposed research are to learn more of the mode of biogenic amine storage and release mechanisms, especially in the brain, with a view to a better understanding of the normal utilization of these neurotransmitters and in the actions of drugs including antipsychotic drugs, antidepressants, antiparkinson drugs, central stimulants, hallucinogens and drugs of abuse. Some examples of proposed research: 1) Investigation of the mode of action of non-amphetamine CNS stimulants. Unlike amphetamine which acts centrally via synthesized catecholamines, amfonelic acid and methylphenidate do not. We have observed a unique action of the latter type of stimulant on facilitation of impulse-induced dopamine release, but not norepinephrine release. We plan to examine further this mode of drug action and extend it to studies with hallucinogens. 2. Differential biochemical action of antipsychotics. We will examine further our findings with clozapine which facilitates impulse-induced norepinephrine release but which may under certain conditions inhibit dopamine release in the corpus striatum and will extend the study to the dopamine mesolimbic areas. 3. Dopamine metabolism and granule function. We will examine further the prime functional role of newly synthesized dopamine and investigate the metabolic routes of newly synthesized versus stored amine, especially as related to storage granule integrity. 4. The reserpine receptor and amine granule function. Using bound reserpine as a specific amine granule marker, we plan to investigate factors controlling granule formation peripherally and in various brain areas. 5. The extragranular neuronal amine binding site. We will extend our investigation of this site which appears to be also the site of binding of adrenergic neuron blocking drugs. We will search for a similar site in central neurons.